BNT162b2 mRNA 疫苗在体外和体内都能降低年龄相关的 TH1 支持率

IF 4.6 2区综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES

iScience Pub Date : 2024-11-15 DOI:10.1016/j.isci.2024.111055

Byron Brook , Abhinav Kumar Checkervarty , Soumik Barman , Cali Sweitzer , Anna-Nicole Bosco , Amy C. Sherman , Lindsey R. Baden , Elena Morrocchi , Guzman Sanchez-Schmitz , Paolo Palma , Etsuro Nanishi , Timothy R. O’Meara , Marisa E. McGrath , Matthew B. Frieman , Dheeraj Soni , Simon D. van Haren , Al Ozonoff , Joann Diray-Arce , Hanno Steen , David J. Dowling , Ofer Levy

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引用次数: 0

摘要

mRNA 疫苗在易受影响的老年人群中显示出免疫原性和持久性受损。我们假设人体体外建模和蛋白质组学可以阐明特定年龄的 mRNA 疫苗作用。BNT162b2 刺激改变了年轻人（18-50 岁）和老年人（≥60 岁）血液样本的血浆蛋白质组，并通过质谱分析、近距离延伸测定和多重分析进行了评估。年轻人的上调（如 PSMC6、CPN1）与老年人的诱导减少（如 TPM4、APOF、APOC2、CPN1、PI16）形成鲜明对比。老年人血液中诱导的 TH1 极化细胞因子和趋化因子（如 IFNγ、CXCL10）降低了 30-85%。老年人样本中含量较低的分析物包括人体内 mRNA 免疫原性生物标记物（如 IFNγ、CXCL10、CCL4、IL-1RA）。BNT162b2 还显示，老年小鼠与年轻成年小鼠的 CD4+ TH1 反应减少。我们的研究证明了人类体外平台模拟年龄特异性 mRNA 疫苗免疫原性的实用性，强调了老年人对 TH1 极化的支持受损，并为精确 mRNA 疫苗佐剂诱导更大的免疫原性提供了理论依据。

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The BNT162b2 mRNA vaccine demonstrates reduced age-associated TH1 support in vitro and in vivo

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The BNT162b2 mRNA vaccine demonstrates reduced age-associated TH1 support in vitro and in vivo

mRNA vaccines demonstrate impaired immunogenicity and durability in vulnerable older populations. We hypothesized that human in vitro modeling and proteomics could elucidate age-specific mRNA vaccine actions. BNT162b2-stimulation changed the plasma proteome of blood samples from young (18-50Y) and older adult (≥60Y) participants, assessed by mass spectrometry, proximity extension assay, and multiplex. Young adult up-regulation (e.g., PSMC6, CPN1) contrasted reduced induction in older adults (e.g., TPM4, APOF, APOC2, CPN1, PI16). 30–85% lower T_H1-polarizing cytokines and chemokines were induced in elderly blood (e.g., IFNγ, CXCL10). Analytes lower in older adult samples included human in vivo mRNA immunogenicity biomarkers (e.g., IFNγ, CXCL10, CCL4, IL-1RA). BNT162b2 also demonstrated reduced CD4⁺ T_H1 responses in aged vs. young adult mice. Our study demonstrates the utility of human in vitro platforms modeling age-specific mRNA vaccine immunogenicity, highlights impaired support of T_H1 polarization in older adults, and provides a rationale for precision mRNA vaccine adjuvantation to induce greater immunogenicity.

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来源期刊

iScience Multidisciplinary-Multidisciplinary

CiteScore

7.20

自引率

1.70%

发文量

1972

审稿时长

6 weeks

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